High blood compatibility is demanded for medical instruments which directly contact body fluid, such as artificial blood vessels, catheters, blood bags, contact lenses, intraocular lenses and artificial kidneys. In addition, it is also important that the blood compatibility of the medical instruments do not deteriorate or denature before the instruments are actually used.
Sterilization is required for most medical instruments. Because of the low residual toxicity and simplicity, radiation sterilization is widely used. On the other hand, since radiation sterilization is a high energy treatment, there is a problem in that it causes deterioration or denaturation of the materials constituting the medical instruments.For example, it is known the effect of polyvinylpyrrolidone which is blended for giving blood compatibility to separation membranes is reduced by excessive crosslinkage or denaturation by the radiation (Non-patent Literature 1).
To reduce denaturation at the time of radiation sterilization, a method has been disclosed, in which a material is impregnated with a solution of an antioxidant such as sodium pyrosulfite (Patent Literature 2). A method in which a material is sterilized with γ-ray in the presence of glycerin (Patent Literature 3) and a method in which the material is sterilized with γ-ray in the presence of a dihydric alcohol such as polypropylene glycol (Patent Literature 4) have also been disclosed. Further, a method has been disclosed, in which a material having a low antithrombogenicity is subjected to radiation sterilization in the presence of a hydrophilic polymer and an antioxidant, thereby grafting the hydrophilic polymer to the material while inhibiting the excess denaturation of the hydrophilic polymer (Patent Literature 5).
These additives aim at inhibiting denaturation at the time of radiation, and the references are totally silent about the stabilization with time after the sterilization. Since a small amount of radicals remain after the radiation sterilization, there is a concern that materials constituting medical instruments denature during storage for a long time so that the blood compatibility is decreased. That is, even though the deterioration or denaturation of medical instruments at the time of radiation sterilization may be inhibited, the blood compatibility may have been deteriorated when the medical instruments are actually used.
On the other hand, as for the stability of medical instruments after radiation sterilization, a method has been disclosed, in which the amount of radicals contained in a membrane is made to be a prescribed level or less in blood purifiers (Patent Literature 6). In this method, excess hydrophilic polymers which may serve as sources of the radicals are removed. However, even if the excess hydrophilic polymers are removed, since some amounts of the hydrophilic polymers remain on the surface, the influence by the residual radicals cannot be avoided.
A method has also been disclosed, in which a chelating agent is added to a spinning solution in order to prevent a small amount of heavy metals from causing generation of radicals, which heavy metals are contaminated into the products during the membrane-forming step in the production of blood-purifying membranes (Patent Literatures 7 and 8). However, generation of radicals by the high energy of the radiation cannot be prevented, which radicals are directly generated in the membranes or generated by hydroxyl radicals generated from the ambient water molecules.
Thus, all of these methods are for inhibiting the generation of radicals by the radiation irradiation, and the material is not a radical-resistant material, so that they do not provide a fundamental solution. Thus, to develop a blood-compatible material having a high radical resistance was demanded, with which the above-mentioned deterioration of the blood compatibility does not occur, and which exhibits high blood compatibility even when the material is irradiated with a radiation at a dose several times the dose necessary for the sterilization.    Patent Literature 1: JP-A-H9-323031    Patent Literature 2: JP-B-2754203    Patent Literature 3: JP-B-2672051    Patent Literature 4: JP-B-3107983    Patent Literature 5: Japanese Republished International Publication No. WO04-018085    Patent Literature 6: JP-A-2000-296318    Patent Literature 7: JP-A-2005-334319    Patent Literature 8: JP-A-2005-342411